Macrophage activation and leishmanicidal activity by galactomannan and its oxovanadium (IV/V) complex in vitro

摘要

Compounds that activatemacrophage antimicrobial activity are potential targets for treatment of leishmaniasis. The present study investigated the in vitro immunomodulatory effects of a galactomannan (GALMAN-A) isolated from seeds of Mimosa scabrella and its oxovanadium (IV/V) complex (GALMAN-A:VO~(2+)/VO~(3+)) on macrophage activity. GALMAN-A increased nitric oxide levels by ~33% at a concentration of 250μg/ml,while GALMAN-A:VO~(2+)/VO~(3+) decreased nitric oxide levels by ~33% at a concentration of 50μg/ml. Furthermore, GALMAN-A increased interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels by 5.5 and 2.3 times, respectively, at a concentration of 25μg/ml; at the same concentration, GALMAN-A:VO~(2+)/VO~(3+) promoted an increase in IL-1β and IL-6 production by 8 and 5.5 times, respectively. However, neither GALMAN-A nor GALMAN-A:VO~(2+)/VO~(3+) affected tumor necrosis factor alpha (TNF-α) or interleukin-10 (IL-10) levels. Importantly, both GALMAN-A and GALMAN-A:VO~(2+)/VO~(3+) exhibited leishmanicidal activity on amastigotes of Leishmania (L.) amazonensis, reaching ~60% activity at concentrations of 100 and 25 μg/ml, respectively. These results indicate that GALMAN-A is three times more potent and its oxovanadium complex is twelve times more potent than Glucantime (300 μg/ml), which is the drug of choice in leishmaniasis treatment. The IC50 value for GALMAN-A:VO~(2+)/VO~(3+) was 74.4 μg/ml (0.58 μg/ml of vanadium). Thus, the significant activation of macrophages and the noted leishmanicidal effect demonstrate the need for further studies to clarify the mechanisms of action of these compounds.